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Filter articles published since 2015 by topic, disease, or article type.

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For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]

Oligodendrocytes May Help SOD1 Take Root in ALS

Spreading the misfolded SOD1? Oligodendrocytes (green) may contribute to ALS by serving as a conduit for mutant SOD1 in the central nervous system (Thomas et al., 2017). [Image: R. Douglas Fields and Hiroaki Wake, Science.]

Oligodendrocytes may facilitate the spread of at least one form of ALS according to a new study led by Yale University’s Arthur Horwich. The study, published on March 16 in the Proceedings of the National Academy of Sciences, found that fluorescent-tagged mutant SOD1 may travel from motor neurons to mature oligodendrocytes in the grey matter of the spinal cord in G85R SOD1 CYP – G85R SOD1 YFP chimeric mice. No transfer, however, could be detected in the brain in either the motor cortex (layer V) or the corpus callosum.

The results suggest that mutant SOD1 might be transmitted between motor neurons and oligodendrocytes, at least in the lumbar spinal cord. The findings build on a previous study led by Nationwide Children’s Hospital’s Brian Kasper in Columbus, Ohio which suggested that neighboring oligodendrocytes contribute to motor neuron degeneration through a SOD1-based mechanism (see November 2016 news; Ferraiuolo et al., 2016).

The study adds to growing evidence that misfolded SOD1 may be transmitted between neurons in the central nervous system through exosome-dependent and independent mechanisms (Ayers et al., 2014; Ayers et al., 2016; Bidhendi et al., 2016; Grad et al., 2014). The results are to be presented by first author Eleanor Thomas at the 2017 meeting of the American Academy of Neurology.

Researchers proposed in 2011 that ALS may spread through a prion-like mechanism. The study, led by Neil Cashman, found that misfolded mutant SOD1 could trigger the misfolding of the properly folded enzyme (Grad et al., 2011). What’s more, misfolded SOD1 could be transmitted between neurons and propagate in vivo (Grad et al., 2014; Munch et al., 2014; Ayers et al., 2014). This propagation according to studies led by University of Florida’s David Borchelt may explain how ALS spreads spatially and temporally– at least in SOD1-linked disease (see January 2016 and March 2017 news; Ayers et al., 2016).

In more recent years, researchers discovered that other ALS-linked proteins could travel between motor neurons and therefore may facilitate the spread of the disease. These include TDP-43 and C9orf72 ALS-associated dipeptide repeat proteins, key proteins involved in the most common forms of the disease (see November 2016 news; Nonaka et al., 2013; Westergard et al., 2016; Zhou et al., 2017). The role of this intercellular transmission of these potentially toxic proteins in the pathogenesis of ALS remains unclear.

Now, Horwich’s team is studying the oligodendrocytes in these mice to determine whether these glial cells facilitate the spread of ALS by helping to transfer mutant SOD1 between motor neurons. Stay tuned.

Filter articles published since 2015 by topic, disease, or article type.

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For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]